Thermolability characteristics and inheritance of human red cell nucleoside triphosphate pyrophosphohydrolase

Biochemical and genetic data which serve to define further the variation of nucleoside triphosphate pyrophosphohydrolase (NTPH) activity in red cells are presented [see also Verhoef, V.L., Fuller, S.A., and Morris, A.J. (1980). Biochem. Genet. 18:235; Soder, C., Henderson, J.F., Zombor, G., McCoy, E. E., Verhoef, V., and Morris, A. J. (1976). Can. J. Biochem. 54:843]. Examination of the in vivo stability of red cell NTPH via separation of cells by density (age) reveals that loss of NTPH activity during the lifetime of the erythrocytes is the same in individuals with high and low NTPH specific activity. However, when the thermolability of lysate NTPH was measured, three phenotypes could be distinguished. In order of decreasing thermolability, these correspond to NTPH specific activities of 0-5, 12-25, and greater than 25. These data provide the first evidence of physical differences in the molecules of NTPH associated with the various specific activities of NTPH present in the human population. Family data are also presented which show that the mode of inheritance of differences in NTPH specific activity cannot be ascribed to a simple autosomal one gene-two allele system. We propose alternatively that the family data conform well to an hypothesis of three alleles at one NTPH locus controlling NTPH activity.